George Washington University Medical Center proposes to establish as AIDS-CSG for performing rapid turnover phase I/II trials of promising 2 drug combinations for the treatment of different stages of HIV-infection (eg. AIDS, ARC, LAS). Initially, 3 proposed 8-14 month trials will be performed, each involving 20- 30 patients; 1) a combination of an anti-viral drug and an immunorestorative drug; Project #1 Ribavirin (escalating + Isoprinosine in HIV-Viremic Patients with LAS, and 2) 2 different combinations of anti-viral drugs that inhibit HIV-replication by different mechanisms, Project #2 AZT - Alpha Interferon (escalating) in Patients with AIDS-related Kaposi's sarcoma without prior opportunistic infections, and Project #3 Low dose AZT + Ampligen (escalating) in patients with AIDS (post-PCP) or late ARC (CD4 less than 200/mm3). Each of the trails will assess the toxicities and clinical efficacy of the drug combinations as well as their virologic and immunologic effects. Dose escalations of 1 of the drugs are included in each protocol to establish optimal dosing. Rigid, but simple criteria are defined with which to judge safety, and clinical, immunologic, and virologic efficacy. Serial laboratory monitoring will include quantitative HIV- isolation by co-culture, serum p24 antigen, quantitative serum HIV-antibody and neutralizing antibody, CD4 and CD8 cell levels, as well as immune functions (eg. lymphoproliferative responses, NK activity) and DTHS skin tests. Based on the results on the pilot studies, we would subsequently participate in the design and performance of large scale randomized trails, with other NIH- funded AIDS-CSG's, to establish whether the 2 drug combinations are superior to each of the single drugs in improving patient survival and/or preventing CDC-defined AIDS. We would also continue to design and implement 2 or 3 drug combination pilot trails using these and other promising drugs such as ddc, and IL-2.